P-Glycoprotein and Androgen Receptor Expression Reveals Independence of Canine Prostate Cancer from Androgen Hormone Stimulation.

Canine prostate cancer (PC) is an aggressive disease, and dogs can be considered comparative models for human PC. In recent years, canine PC has been shown to resemble human castrate-resistant prostate cancer. The influx and efflux of testosterone in prostatic luminal cells are regulated by P-glycoprotein (P-gp). Therefore, human PC generally lacks P-gp expression and maintains the expression of androgen receptors (ARs). However, this co-expression has not previously been investigated in dogs. Therefore, this study aimed to evaluate AR and P-gp co-expression to elucidate these protein patterns in canine prostate samples. We identified AR/P-gp double immunofluorescence co-expression of both proteins in normal luminal cells. However, in canine PC, cells lack AR expression and exhibit increased P-gp expression. These results were confirmed by gene expression analyses. Overall, our results strongly suggest that normal canine prostate testosterone influx may be regulated by P-gp expression, and that during progression to PC, prostatic cells lack AR expression and P-gp overexpress. P-gp expression in canine PC may be related to a phenotype of multiple drug resistance.

Expression and prognostic significance of vascular endothelial growth factor-A (VEGF-A) and its receptor in canine prostate cancer.

BACKGROUND: Vascular endothelial growth factor-A (VEGF-A) and its receptor, VEGF receptor-2 (VEGFR-2), represent a complex family of angiogenic molecules consisting of different ligands and receptors. Due to the importance of VEGF-A/VEGFR-2 signaling in tumor proliferation and angiogenesis, this study aimed to evaluate the protein and gene expression levels of VEGF-A and VEGFR-2 in canine prostate cancer (PC). METHODS: We analyzed VEGF-A and VEGFR-2 expression in 87 PC samples by immunohistochemistry and quantitative-polymerase chain reaction. PC samples were graded according to the Gleason score and the immunohistochemical staining for VEGF-A and VEGFR-2 was quantified using a selected threshold from the ImageJ Software. Microvascular density was assessed by cluster of differentiation 31 staining and counting the number of positive vessels. Additionally, the homology of VEGF-A and VEGFR-2 between humans and dogs was assessed, followed by the construction of a protein structure homology model to compare the tertiary structures of these proteins in both species. RESULTS: Negative to weakly positive expression levels of VEGF-A and VEGFR-2 were observed in the epithelial cells of the normal prostate (NP) and prostatic hyperplasia samples. In contrast, the canine proliferative atrophy and PC samples exhibited higher VEGF-A (p < .0001) and VEGFR-2 (p < .0001) compared to NP. Moreover, positive correlations between the expression levels of VEGF-A and VEGFR-2 (Spearman's coefficient (r) = .68, p = .013) and the expression levels of VEGF-A and VEGFR-2 proteins (r = .8, p < .0001) were also observed in the NP samples. Additionally, the patients with PC exhibiting higher VEGFR-2 expression levels experienced a shorter survival period (p = .0372). Furthermore, we found an association between the microvascular density and overall survival. Dogs with a higher number of vessels showed a shorter survival time. We further demonstrated that the VEGF-A and VEGFR-2 exhibited high homology between humans and dogs, and identified their protein structures in both species. CONCLUSIONS: In conclusion, VEGFR-2 appears to be an independent prognostic factor in animals with PC. VEGF-A and VEGFR-2 are highly conserved between humans and dogs, which can be investigated further in future cross-species studies to explore their therapeutic applications.

Endometrial angiogenesis induced by uterine insufflation with an oxygen-ozone gas mixture in mares.

Ozone (O3 ) therapy has been used to improve peripheral tissue oxygenation in humans and domestic animals. The goal of the present study was to characterize histological changes in the endometria of healthy equines following tissue exposure to gas mixtures enriched with different concentrations of O3 . Cycling mares without endometrial degeneration were divided into three groups according to treatment (n = 9 mares/group). The uteri from the O3 , ½O3 and control groups were insufflated for 3 min with gas containing 42, 21 and 0 µg O3 ml-1 , respectively. Treatments were performed every three days from D0 to D6. Endometrial samples were collected immediately before the first treatment and 24 hr after the last treatment. The following nine histological parameters were evaluated: (i) the number of endometrial blood vessels, (ii) endometrial vascular degree (EVD), (iii) increase rate of blood vessels, (iv) increase rate of EVD, (v) glandular total area, (vi) glandular lumen area, (vii) intraglandular secretion area, (viii) glandular epithelial height and (ix) luminal epithelial height. In the O3 group, a positive effect from treatment (p < .01) was detected for all vascular parameters (i, ii, iii and iv), glandular total area, intraglandular secretion area and glandular epithelial height. Compared to the control group, the ½O3 group had greater (p < .01) EVD (84.1 ± 12%) and a higher increase rate of blood vessels (151.9 ± 47.1%). Uterine insufflation with low or intermediate concentrations of the O2 -O3 gas mixture induced endometrial angiogenesis. Morphometry, but not morphology, of the endometrial glands was affected by local O3 therapy. These findings would be of great significance for the development of new therapies for infertility in mares.

Comprehensive Genomic Profiling of Androgen-Receptor-Negative Canine Prostate Cancer.

Canine carcinomas have been considered natural models for human diseases; however, the genomic profile of canine prostate cancers (PCs) has not been explored. In this study, 14 PC androgen-receptor-negative cases, 4 proliferative inflammatory atrophies (PIA), and 5 normal prostate tissues were investigated by array-based comparative genomic hybridization (aCGH). Copy number alterations (CNAs) were assessed using the Canine Genome CGH Microarray 4 × 44K (Agilent Technologies). Genes covered by recurrent CNAs were submitted to enrichment and cross-validation analysis. In addition, the expression levels of TP53, MDM2 and ZBTB4 were evaluated in an independent set of cases by qPCR. PC cases presented genomic complexity, while PIA samples had a small number of CNAs. Recurrent losses covering well-known tumor suppressor genes, such as ATM, BRCA1, CDH1, MEN1 and TP53, were found in PC. The in silico functional analysis showed several cancer-related genes associated with canonical pathways and interaction networks previously described in human PC. The MDM2, TP53, and ZBTB4 copy number alterations were translated into altered expression levels. A cross-validation analysis using The Cancer Genome Atlas (TCGA) database for human PC uncovered similarities between canine and human PCs. Androgen-receptor-negative canine PC is a complex disease characterized by high genomic instability, showing a set of genes with similar alterations to human cancer.

Investigation of c-KIT and Ki67 expression in normal, preneoplastic and neoplastic canine prostate.

BACKGROUND: c-KIT expression has been related to bone metastasis in human prostate cancer, but whether c-KIT expression can be similarly classified in canine prostatic tissue is unknown. This study assessed c-KIT and Ki67 expression in canine prostate cancer (PC). c-KIT gene and protein expression and Ki67 expression were evaluated in forty-four canine prostatic tissues by immunohistochemistry, RT-qPCR and western blot. Additionally, we have investigated c-KIT protein expression by immunoblotting in two primary canine prostate cancer cell lines. RESULTS: Eleven normal prostates, 12 proliferative inflammatory atrophy (PIA) prostates, 18 PC, 3 metastatic lesions and two prostate cancer cell cultures (PC1 and PC2) were analysed. The prostatic tissue exhibited varying degrees of membranous, cytoplasmic or membranous/cytoplasmic c-KIT staining. Four normal prostates, 4 PIA and 5 prostatic carcinomas showed positive c-KIT expression. No c-KIT immunoexpression was observed in metastases. Canine prostate cancer and PIA samples contained a higher number of Ki67-positive cells compared to normal samples. The median relative quantification (RQ) for c-KIT expression in normal, PIA and prostate cancer and metastatic samples were 0.6 (0.1-2.5), 0.7 (0.09-2.1), 0.7 (0.09-5.1) and 0.1 (0.07-0.6), respectively. A positive correlation between the number of Ki67-positive cells and c-KIT transcript levels was observed in prostate cancer samples. In the cell line, PC1 was negative for c-KIT protein expression, while PC2 was weakly positive. CONCLUSION: The present study identified a strong correlation between c-KIT expression and proliferative index, suggesting that c-KIT may influence cell proliferation. Therefore, c-KIT heterogeneous protein expression among the samples (five positive and thirteen negative prostate cancer samples) indicates a personalized approach for canine prostate cancer.

Spontaneous poisoning by Hovenia dulcis in dairy cattle in Southwest Parana, Brazil.

Livestock poisoning by plants is a frequent occurrence which determines severe losses, such as the fall in the milk and meat production, the cost of expensive treatments, the state of immunosuppression, or even the animal's death. Cattle ingest toxic plants only when there is food shortage, when they cannot select what they eat, or when they ingest food for preference, which is the case of Hovenia dulcis fruits, very rich in sucrose. This plant is widely distributed in the southern and southeastern Brazilian regions. In literature, there are some cases of severe human liver injury associated with a long-term of H. dulcis leaf and fruit tea intake, and only one report regarding spontaneous poisoning of goats caused by this plant ingestion. However, its toxic effects associated with spontaneous ingestion by cattle have never been reported. This paper reports the first case of spontaneous poisoning in cattle by H. dulcis, which occurred in a dairy farm in southwest Paraná, Brazil. Three cattle individuals showed anorexia, ruminal atony, severe diarrhea and neurological tournament, head pressing, blindness, ataxia, and circling. The necropsy of the animals was done, and the remaining alterations were restricted to the digestive system and brain. The clinical signs presented by the animals are characteristic of polioencephalomalacia (PEM), caused by changes in the thiamine metabolism. Furthermore, clinical signs, gross, and microscopic lesions as well as the large amount of the plant throughout the digestive segment led to a diagnosis.

Lapatinib antitumor effect is associated with PI3K and MAPK pathway: An analysis in human and canine prostate cancer cells.

The aberrant activation of HER2 has a pivotal role in bone metastasis implantation and progression in several tumor types, including prostate cancer (PC). Trastuzumab and other anti-HER2 therapies, such as lapatinib, have been used in human breast cancer HER2 positive. Although HER2 overexpression has been reported in PC, anti-HER2 therapy response has revealed conflicting results. We investigated the potential of lapatinib in inhibiting cell migration and inducing apoptosis in two human (LNCaP and PC3) and two canine PC cell lines (PC1 and PC2). Cell migration and apoptosis were evaluated by Annexin V/PI analysis after lapatinib treatment. The transcriptome analysis of all cell lines before and after treatment with lapatinib was also performed. We found increased apoptosis and migration inhibition in LNCaP cells (androgen-sensitive cell line), while PC1, PC2, and PC3 cells showed no alterations after the treatment. The transcriptome analysis of LNCaP and PC3 cell lines showed 158 dysregulated transcripts in common, while PC1 and PC2 cell lines presented 82. At the doses of lapatinib used, we observed transcriptional modifications in all cell lines. PI3K/AKT/mTOR pathway were enriched in human PC cells, while canine PC cells showed enrichment of tyrosine kinase antitumor response and HER2-related pathways. In canine PC cells, the apoptosis failed after lapatinib treatment, possibly due to the downregulation of MAPK genes. Prostate cancer cells insensitive to androgens may be resistant to lapatinib through PI3K gene dysregulation. The association of lapatinib with PI3K inhibitors may provide a more effective antitumor response and clinical benefits to PC patients.

Background and common lesions in the female reproductive organs of giant anteaters (Myrmecophaga tridactyla).

The giant anteater (Myrmecophaga tridactyla) is a vulnerable species in South America and is considered endangered or near extinction in Central America. Therefore, studies describing the reproductive characteristics of this species are pivotal for its conservation. Thus, this study aimed to provide a morphological description of the female reproductive tissues of this species. We collected tissue samples from six female giant anteaters and performed gross, morphological, and histochemical analyses. Five adult subjects and one juvenile were included in the study. In the ovary, classifications were made according to the follicle and oocyte sizes: primordial, primary, secondary, early antral, or antral. Typical follicles with a single oocyte surrounded by a simple or stratified layer of cubic epithelium, atretic follicles, corpora lutea, corpora albicans, and ovarian cysts were also observed. No ovarian lesions were observed. By contrast, endometritis, metritis, mucometra, and endometrial cysts were identified in the uterus. Uterine alterations in these subjects were frequent and could affect reproduction.

Is Osteopontin a Good Marker for Bone Metastasis in Canine Mammary Gland Tumor and Prostate Cancer?

Osteopontin (OPN) is a protein synthesized by a large number of cells, and its overexpression has been associated with the development and prognosis of cancer. OPN overexpression has been claimed to be a marker for the development of bone metastasis in human cancers, but no prior research has investigated the association between OPN expression and the metastasis of canine mammary gland tumors (MGTs) and prostate cancer (PC). Therefore, we investigated OPN expression in MGTs and PC samples from 50 canine patients with or without metastasis (bone vs. other sites). Higher OPN expression was detected in primary tumor samples from animals with bone metastasis than in those without bone involvement (p = 0.0321). In MGT samples, a significantly lower survival rate was observed in patients with higher OPN expression (p = 0.0171). In animals with PC, there was a strong trend toward lower survival in animals with positive OPN expression; however, this trend was not statistically significant (p = 0.0779). From these findings, it can be concluded that OPN may be a promising target for future MGTs and PC studies because of its role in enhancing cell invasion and metastasis.

Proposing Clinicopathological Staging and Mitotic Count as Prognostic Factors for Canine Soft Tissue Sarcomas.

Soft tissue sarcomas (STSs) are a heterogeneous group of malignant mesenchymal tumors with similar histological features and biological behaviors. They are characterized by a low to moderate local recurrence rate and low metastasis, affecting approximately 20% of patients. Although this tumor set is vital in veterinary medicine, no previous unified staging system or mitotic count has been associated with patient prognosis. Therefore, this study proposed a new clinicopathological staging method and evaluated a cut-off value for mitosis related to the survival of dogs affected by STS. This study included 105 dogs affected by STS, treated only with surgery, and a complete follow-up evaluation. The new clinicopathological staging system evaluated tumor size (T), nodal involvement (N), distant metastasis (M), and histological grading criteria (G) to categorize the tumor stage into four groups (stages I, II, III, and IV). The proposed tumor staging system was able to differentiate patients' prognoses, with dogs with stage IV disease experiencing the lowest survival time and dogs with stage I disease having the highest survival time (p < 0.001). Moreover, we assessed the median mitosis (based on mitotic count) and its association with overall survival. Our study's median mitosis was 5, and patients with ≤5 mitoses had a higher survival time (p = 0.006). Overall, the proposed staging system and mitotic count seemed promising in the prediction of patient prognosis.

Canine urothelial carcinoma: expression of Periostin in spontaneous canine urothelial carcinoma and its correlation with histological features.

The tumor microenvironment is considered one of the main players in cancer development and progression and may influence the behavior of cancer cells. Periostin (POSTN) is an extracellular matrix protein, and its main functions are induction of fibrillogenesis, fibroblastic cell proliferation and migration, enhancing regeneration in normal tissue, and promoting metastasis in case of neoplasia. POSTN has already been studied in humans in several normal tissues, inflammatory processes, and neoplasms, revealing an important role in tumor progression in various types of cancer, such as colon, lung, head and neck, breast, ovarian, and prostate. In these latter, high levels of POSTN are usually associated with a more aggressive tumor behavior, tumor advanced stages, and poor prognosis, while in human bladder urothelial carcinoma (BUC), unlike in most tumors, POSTN expression seems to be downregulated. The expression of this marker has been poorly investigated in veterinary medicine; thus, this study aimed to immunohistochemically investigate the presence and the intensity of POSTN expression in canine BUCs and to determine a possible relationship between POSTN expression and histopathological features such as mitotic count and muscular and vascular invasions. For the present retrospective study, archived samples from 45 canine BUCs and 6 non-neoplastic canine bladders were considered for histological evaluation and immunohistochemical examination for the expression of POSTN. POSTN expression was semi-quantitatively assessed considering both the percentage of the neoplastic stroma positive for POSTN and the intensity of the immunohistochemical labeling. Histologically, 38 out of 45 tumors were papillary and 7 out of 45 were non-papillary. All tumors were infiltrating, being that 21 were muscle-invasive, and a significant correlation between this feature and vascular invasion emerged (P = 0.0001). In normal bladder tissue, as reported in humans, a thick and strongly positive belt of POSTN was visible, and in canine BUCs, stating that the expression is comparable with human benign as well as malignant bladder tissue, a general decrease in POSTN expression was observed except for a strongly labeled ring of POSTN observed around some neoplastic nodules infiltrating the muscle layer. Moreover, POSTN expression and mitotic count were significatively inversely correlated (P = 0.0015). The fact that POSTN protein is less expressed in urothelial carcinomas than in the normal bladder supports what was reported in human BUCs and, together with the negative correlation between mitotic count and protein expression that emerged in the present retrospective study, encourages further prospective follow-up studies to verify the possible role of POSTN in canine BUCs as a prognostic marker, and also as a possible target for the development of future anticancer therapies.

Biocompatibility of hydrogel derived from equine tendon extracellular matrix in horses subcutaneous tissue.

Tendinopathies account for a substantial proportion of musculoskeletal injuries. To improve treatment outcomes for partial and total tendon ruptures, new therapies are under investigation. These include the application of mesenchymal stem cells (MSCs) and biocompatible scaffolds derived from the Extracellular Matrix (ECM). Synthetic polymer hydrogels have not demonstrated results as promising as those achieved with ECM hydrogels sourced from the original tissue. This study aimed to evaluate the biocompatibility of a hydrogel formulated from equine tendon ECM. Six horses were administered three subcutaneous doses of the hydrogel, with a saline solution serving as a control. Biopsies were conducted on days 7, 14, and 56 post-application to gauge the hydrogel's impact. Throughout the experiment, the horse's physical condition remained stable. Thermographic analyses revealed a temperature increase in the treated groups compared to the control group within the initial 12 h. The von Frey test, used to measure the mechanical nociceptive threshold, also showed significant differences between the treated group and the control group at 6 h, 21 days, and 28 days. Histopathological analyses identified an inflammatory response on day 7, which was absent on days 14 and 56. Transmission electron microscopy indicated a decrease in inflammatory cellularity, while immunohistochemistry staining suggested an increased presence of inflammatory factors on day 14. In summary, the hydrogel is easily injectable, triggers a temporary local inflammatory response, and integrates into the adjacent tissue from day 14 onwards.

Diagnosis, Prognosis, and Treatment of Canine Hemangiosarcoma: A Review Based on a Consensus Organized by the Brazilian Association of Veterinary Oncology, ABROVET.

Hemangiosarcoma is a mesenchymal neoplasm originating in the endothelial cells of blood vessels; they can be classified as non-visceral and visceral types. Non-visceral hemangiosarcomas can affect the skin, subcutaneous tissues, and muscle tissues; visceral hemangiosarcomas can affect the spleen, liver, heart, lungs, kidneys, oral cavity, bones, bladder, uterus, tongue, and retroperitoneum. Among domestic species, dogs are most affected by cutaneous HSA. Cutaneous HSA represents approximately 14% of all HSA diagnosed in this species and less than 5% of dermal tumors, according to North American studies. However, Brazilian epidemiological data demonstrate a higher prevalence, which may represent 27 to 80% of all canine HSAs and 13.9% of all skin neoplasms diagnosed in this species. Cutaneous HSA most commonly affects middle-aged to elderly dogs (between 8 and 15 years old), with no gender predisposition for either the actinic or non-actinic forms. The higher prevalence of cutaneous HSA in some canine breeds is related to lower protection from solar radiation, as low skin pigmentation and hair coverage lead to greater sun exposure. Actinic changes, such as solar dermatosis, are frequent in these patients, confirming the influence of solar radiation on the development of this neoplasm. There are multiple clinical manifestations of hemangiosarcoma in canines. The diagnostic approach and staging classification of cutaneous HSAs are similar between the different subtypes. The definitive diagnosis is obtained through histopathological analysis of incisional or excisional biopsies. Cytology can be used as a presurgical screening test; however, it has little diagnostic utility in cases of HSA because there is a high risk of blood contamination and sample hemodilution. Surgery is generally the treatment of choice for dogs with localized non-visceral HSA without evidence of metastatic disease. Recently, electrochemotherapy (ECT) has emerged as an alternative therapy for the local ablative treatment of different neoplastic types; the use of radiotherapy for the treatment of dogs with cutaneous HSA is uncommon. There is greater consensus in the literature regarding the indications for adjuvant chemotherapy in subcutaneous and muscular HSA; doxorubicin is the most frequently used antineoplastic agent for subcutaneous and muscular subtypes and can be administered alone or in combination with other drugs. Other therapies include antiangiogenic therapy, photodynamic therapy, the association of chemotherapy with the metronomic dose, targeted therapies, and natural products. The benefits of these therapies are presented and discussed. In general, the prognosis of splenic and cardiac HSA is unfavorable. As a challenging neoplasm, studies of new protocols and treatment modalities are necessary to control this aggressive disease.

A Review on Canine and Feline Prostate Pathology.

Prostatic diseases are very common in male dogs, accounting for 3-10% of cases submitted to the veterinary practitioners. Commonly reported canine prostatic disorders include prostatic hyperplasia, prostatitis, prostatic cysts and prostatic carcinoma. However, clinical signs may be non-specific, or many cases are asymptomatic, thus leading to a difficult estimation of the actual prevalence of clinical cases. On the other side, because of the rare occurrence of prostate disease in cats, very little is known about pathogenesis, diagnostic approaches and treatment. The goal of this review is to provide detailed clinical and pathological overview of the feline and canine prostatic pathology, including the most up-to-date classification systems and histological findings. Emphasis is places on gross, cytological and histological features that are critical to reach a definitive diagnosis for a proper treatment and prognosis.

The use of flow cytometry for diagnosis and immunophenotyping in chronic lymphocytic leukemia in a dog: Clinical case report.

Background: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in dogs. It is characterized by the proliferation of neoplastic lymphocytes in the bone marrow, which are morphologically normal (mature), but non-functional. CLL in canines commonly originates in cytotoxic T lymphocytes (TCD8+), and although there is controversy regarding the prognostic value of the immunophenotype, this cell lineage may be associated with a good prognosis. Case Description: A 10-year-old, entire female, mixed-breed dog was brought to the University Hospital of the Veterinary Faculty (UdelaR) for consultation because a routine pre-surgical check-up revealed lymphocytic leukocytosis, normocytic anemia, and hyperglobulinemia due to an oligoclonal gammopathy. The ultrasound revealed splenomegaly. PCR performed on blood was negative for Ehrlichia canis. Blood and bone marrow flow cytometry was performed to complement the diagnosis and carry out the immunophenotype, which showed CLL of CD8+ T-cell lineage. The clinical suspicion of CLL was confirmed by a myelogram. Chemotherapy treatment based on alkylating agents and glucocorticoids was established. So far, the patient has an overall survival of 13 months with a good response to treatment. Conclusion: The combination of the immunophenotyping test, the myelogram, and the hematological and biochemical profile confirmed the presence of T-CLL in our patient. Flow cytometry, increasingly used in veterinary medicine, allowed us to confirm the diagnosis of CLL originating in cytotoxic T lymphocytes in our patient, through the presence of positive staining of primary antibodies specific for the canine species CD45, CD3, CD5, and CD8 and the absence of staining for CD4, CD21, and CD34.

Comparative Pathobiology of Canine and Human Prostate Cancer: State of the Art and Future Directions.

First described in 1817, prostate cancer is considered a complex neoplastic entity, and one of the main causes of death in men in the western world. In dogs, prostatic carcinoma (PC) exhibits undifferentiated morphology with different phenotypes, is hormonally independent of aggressive character, and has high rates of metastasis to different organs. Although in humans, the risk factors for tumor development are known, in dogs, this scenario is still unclear, especially regarding castration. Therefore, with the advent of molecular biology, studies were and are carried out with the aim of identifying the main molecular mechanisms and signaling pathways involved in the carcinogenesis and progression of canine PC, aiming to identify potential biomarkers for diagnosis, prognosis, and targeted treatment. However, there are extensive gaps to be filled, especially when considering the dog as experimental model for the study of this neoplasm in humans. Thus, due to the complexity of the subject, the objective of this review is to present the main pathobiological aspects of canine PC from a comparative point of view to the same neoplasm in the human species, addressing the historical context and current understanding in the scientific field.

Grading Systems for Canine Urothelial Carcinoma of the Bladder: A Comparative Overview.

The relationship between tumor morphology and clinical behavior is a key point in oncology. In this scenario, pathologists and clinicians play a pivotal role in the identification and testing of reliable grading systems based on standardized parameters to predict patient prognosis. Dogs with bladder urothelial carcinoma (BUC) were recently proposed as a "large animal" model for the study of human BUCs due to the similar morphology and metastasis locations. BUC grading systems are consolidated in human medicine, while in veterinary medicine, the BUC grading systems that have been proposed for canine tumors are not yet applied in routine diagnostics. These latter systems have been proposed, decade by decade, over the last thirty years, and the reason for their scarce application is mainly related to a lack of specific cutoff values and studies assessing their prognostic relevance. However, for any prognostic study, reliable grading is necessary. The aim of the present article was to give an overview of the BUC grading systems available in both human and veterinary pathology and provide an extensive description and a critical evaluation to support veterinary researchers in the choice of possible grading systems to apply in future studies on canine BUCs.

Epidemiological characterization of notified human brucellosis cases in Southern Brazil.

Brucellosis is one of the most important and widespread bacterial zoonotic diseases worldwide, and it is transmitted to humans from various sources, including direct contact with infected animals and the ingestion of contaminated products, including unpasteurized milk. There are only a few epidemiological studies on said disease in humans in Western Santa Catarina, a region instantiated by agriculture. Thus, the objective of this study was to characterize the epidemiological aspects of human brucellosis reported in Western Santa Catarina from 2013 to 2018. The data were provided by the Epidemiological Surveillance Board (Diretoria de Vigilancia Epidemiologica). The frequency of the disease in humans and the epidemiological profile of confirmed human cases were evaluated. Cases that were screened positive and those that were confirmed and submitted to the therapeutic protocol were analyzed. During the study period, 3,671 people were tested, of which 12.34% were screened positive (453/ 3,671) and 3.40% were confirmed (125/3,671). The year with the highest number of people testing positive was 2015 (123 cases), and 2018 was the year with the highest number of confirmed cases (39 cases). Confirmed cases predominated in males (48.8%), self-declared white (22.4%), aged 20-59 years old (60%), with incomplete primary education (22.4%), of rural origin (59.2%), with occupational contact with cattle (64.8%), engaged in professions directly linked to agricultural and livestock activities (55.5%), and who reported consumption of unpasteurized dairy products (59.2%). No seasonal variation was observed in case numbers. The results demonstrated that brucellosis is an endemic disease in Western Santa Catarina.